MAX2_CAEEL
ID MAX2_CAEEL Reviewed; 646 AA.
AC G5EGQ3; G5EGS0; H2KMK1; Q9XWL8;
DT 22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Serine/threonine-protein kinase max-2 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:20008556};
DE AltName: Full=Motor axon guidance protein 2 {ECO:0000312|WormBase:Y38F1A.10c};
DE AltName: Full=p21-activated kinase {ECO:0000305|PubMed:17050621};
GN Name=max-2 {ECO:0000312|WormBase:Y38F1A.10c};
GN ORFNames=Y38F1A.10 {ECO:0000312|WormBase:Y38F1A.10c};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:ABF71877.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-388.
RX PubMed=17050621; DOI=10.1242/dev.02648;
RA Lucanic M., Kiley M., Ashcroft N., L'Etoile N., Cheng H.J.;
RT "The Caenorhabditis elegans P21-activated kinases are differentially
RT required for UNC-6/netrin-mediated commissural motor axon guidance.";
RL Development 133:4549-4559(2006).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF GLY-388.
RX PubMed=18499456; DOI=10.1016/j.cub.2008.04.050;
RA Quinn C.C., Pfeil D.S., Wadsworth W.G.;
RT "CED-10/Rac1 mediates axon guidance by regulating the asymmetric
RT distribution of MIG-10/lamellipodin.";
RL Curr. Biol. 18:808-813(2008).
RN [4] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19023419; DOI=10.1371/journal.pgen.1000269;
RA Lucanic M., Cheng H.J.;
RT "A RAC/CDC-42-independent GIT/PIX/PAK signaling pathway mediates cell
RT migration in C. elegans.";
RL PLoS Genet. 4:E1000269-E1000269(2008).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH MLK-1 AND MIG-2,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-388 AND LYS-405.
RX PubMed=20008556; DOI=10.1128/mcb.01131-09;
RA Fujiki K., Mizuno T., Hisamoto N., Matsumoto K.;
RT "The Caenorhabditis elegans Ste20-related kinase and Rac-type small GTPase
RT regulate the c-Jun N-terminal kinase signaling pathway mediating the stress
RT response.";
RL Mol. Cell. Biol. 30:995-1003(2010).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23390595; DOI=10.1534/g3.112.004416;
RA Peters E.C., Gossett A.J., Goldstein B., Der C.J., Reiner D.J.;
RT "Redundant canonical and noncanonical Caenorhabditis elegans p21-activated
RT kinase signaling governs distal tip cell migrations.";
RL G3 (Bethesda) 3:181-195(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase, which phosphorylates mlk-1.
CC Involved in the stress response to heavy metals by activating the mlk-
CC 1/mek-1/kgb-1 pathway (PubMed:20008556). In ventral cord commissural
CC motoneurons, required for dorsal axon guidance downstream of unc-
CC 6/netrin repulsion receptor unc-5 and probably of Rho GTPases ced-10
CC and mig-2. Plays a redundant role with mig-10 in orientating axonal
CC growth of HSN neurons (PubMed:18499456). Plays a redundant role with
CC pak-1 in P neuroblast migration and in distal tip cell (DTC)-mediated
CC guidance of gonad elongation probably downstream of Rho GTPases
CC (PubMed:17050621, PubMed:19023419, PubMed:23390595). In association
CC with pak-2, plays a role in embryogenesis. In association with pak-1,
CC may be involved in spermatogenesis (PubMed:23390595).
CC {ECO:0000269|PubMed:17050621, ECO:0000269|PubMed:18499456,
CC ECO:0000269|PubMed:19023419, ECO:0000269|PubMed:20008556,
CC ECO:0000269|PubMed:23390595}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:20008556};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:20008556};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:20008556};
CC -!- SUBUNIT: Interacts with mlk-1; the interaction is independent of max-2
CC and mlk-1 kinase activities. Interacts with mig-2 (GTP-bound form).
CC {ECO:0000269|PubMed:20008556}.
CC -!- SUBCELLULAR LOCATION: Perikaryon {ECO:0000269|PubMed:17050621}. Cell
CC projection, dendrite {ECO:0000269|PubMed:17050621}. Cytoplasm
CC {ECO:0000269|PubMed:19023419}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=c {ECO:0000312|WormBase:Y38F1A.10c};
CC IsoId=G5EGQ3-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:Y38F1A.10a};
CC IsoId=G5EGQ3-2; Sequence=VSP_057795;
CC Name=b {ECO:0000312|WormBase:Y38F1A.10b};
CC IsoId=G5EGQ3-3; Sequence=VSP_057794;
CC Name=d {ECO:0000312|WormBase:Y38F1A.10d};
CC IsoId=G5EGQ3-4; Sequence=VSP_057793;
CC -!- DEVELOPMENTAL STAGE: Expressed ubiquitously in early embryo. At the
CC comma stage and at later embryonic stages expression is mainly
CC restricted to the anterior region of the embryo and to the ventral
CC cord. At the 1.5-fold embryonic stage, expression starts in pharynx and
CC in several head and tail neurons and is maintained in adults. During L1
CC larval stage, expressed in ALM and PLM neurons and later in PVD and AVM
CC neurons. {ECO:0000269|PubMed:17050621}.
CC -!- DISRUPTION PHENOTYPE: Isoforms a and c: Partial sensitivity to the
CC heavy metal Cu(2+), which is characterized by a failure of larvae to
CC reach adulthood. Partial reduction in basal kgb-1 phosphorylation and
CC after Cu(2+) treatment (PubMed:20008556). Several DD and DC motoneuron
CC axons fail to reach the dorsal cord. RNAi-mediated knockdown causes a
CC similar phenotype but less severe. In max-2 and pak-1 double mutants,
CC defect in axonal guidance is more severe. Animals are also
CC uncoordinated, defective in egg laying and in distal tip cell (DTC)
CC migration, morphology and guidance, and exhibit ventral enclosure
CC defects (PubMed:17050621). A more severe phenotype has been reported
CC where double mutant animals have embryonic morphogenesis defects
CC resulting in lethality. The few surviving adults are sterile and often
CC have truncated gonads which, in some cases, lack sperm. RNAi-mediated
CC knockdown rescues embryonic lethality of pak-1 and pak-2 double mutants
CC (PubMed:23390595). {ECO:0000269|PubMed:17050621,
CC ECO:0000269|PubMed:20008556, ECO:0000269|PubMed:23390595}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; DQ523832; ABF71877.1; -; mRNA.
DR EMBL; BX284602; CAA21637.2; -; Genomic_DNA.
DR EMBL; BX284602; CAL49443.1; -; Genomic_DNA.
DR EMBL; BX284602; CAQ35064.1; -; Genomic_DNA.
DR EMBL; BX284602; CCE71454.1; -; Genomic_DNA.
DR PIR; T26684; T26684.
DR RefSeq; NP_001076635.1; NM_001083166.2. [G5EGQ3-2]
DR RefSeq; NP_001076636.1; NM_001083167.1. [G5EGQ3-3]
DR RefSeq; NP_001122655.1; NM_001129183.2. [G5EGQ3-1]
DR RefSeq; NP_001254363.1; NM_001267434.1. [G5EGQ3-4]
DR AlphaFoldDB; G5EGQ3; -.
DR SMR; G5EGQ3; -.
DR STRING; 6239.Y38F1A.10c; -.
DR PaxDb; G5EGQ3; -.
DR PeptideAtlas; G5EGQ3; -.
DR EnsemblMetazoa; Y38F1A.10a.1; Y38F1A.10a.1; WBGene00003144. [G5EGQ3-2]
DR EnsemblMetazoa; Y38F1A.10b.1; Y38F1A.10b.1; WBGene00003144. [G5EGQ3-3]
DR EnsemblMetazoa; Y38F1A.10c.1; Y38F1A.10c.1; WBGene00003144. [G5EGQ3-1]
DR EnsemblMetazoa; Y38F1A.10d.1; Y38F1A.10d.1; WBGene00003144. [G5EGQ3-4]
DR GeneID; 3565400; -.
DR KEGG; cel:CELE_Y38F1A.10; -.
DR UCSC; Y38F1A.10a; c. elegans.
DR CTD; 3565400; -.
DR WormBase; Y38F1A.10a; CE40478; WBGene00003144; max-2. [G5EGQ3-2]
DR WormBase; Y38F1A.10b; CE35656; WBGene00003144; max-2. [G5EGQ3-3]
DR WormBase; Y38F1A.10c; CE42477; WBGene00003144; max-2. [G5EGQ3-1]
DR WormBase; Y38F1A.10d; CE46596; WBGene00003144; max-2. [G5EGQ3-4]
DR eggNOG; KOG0578; Eukaryota.
DR HOGENOM; CLU_000288_26_2_1; -.
DR InParanoid; G5EGQ3; -.
DR OMA; CANIDGD; -.
DR Reactome; R-CEL-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-CEL-3928664; Ephrin signaling.
DR Reactome; R-CEL-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-CEL-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-CEL-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-CEL-5627123; RHO GTPases activate PAKs.
DR Reactome; R-CEL-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-CEL-9013149; RAC1 GTPase cycle.
DR Reactome; R-CEL-9013407; RHOH GTPase cycle.
DR Reactome; R-CEL-9013420; RHOU GTPase cycle.
DR Reactome; R-CEL-9013424; RHOV GTPase cycle.
DR SignaLink; G5EGQ3; -.
DR PRO; PR:G5EGQ3; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00003144; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; G5EGQ3; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IPI:WormBase.
DR GO; GO:0016477; P:cell migration; IGI:UniProtKB.
DR GO; GO:0035262; P:gonad morphogenesis; IMP:WormBase.
DR GO; GO:0007506; P:gonadal mesoderm development; IEA:UniProtKB-KW.
DR GO; GO:0040039; P:inductive cell migration; IGI:WormBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; IGI:WormBase.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:UniProtKB.
DR GO; GO:0038007; P:netrin-activated signaling pathway; IGI:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:WormBase.
DR GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0046688; P:response to copper ion; IMP:WormBase.
DR Gene3D; 3.90.810.10; -; 1.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell projection; Cytoplasm;
KW Differentiation; Gonadal differentiation; Kinase; Magnesium; Metal-binding;
KW Neurogenesis; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase.
FT CHAIN 1..646
FT /note="Serine/threonine-protein kinase max-2"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433491"
FT DOMAIN 41..54
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 376..627
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 19..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 19..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 244..263
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 266..334
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 496
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 382..390
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 405
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..377
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_057793"
FT VAR_SEQ 1..263
FT /note="MSTSKSSKVRIRNFIGRIFSPSDKDKDRDDEMKPSSSAMDISQPYNTVHRVH
FT VGYDGQKFSGLPQPWMDILLRDISLADQKKDPNAVVTALKFYAQSMKENEKTKFMTTNS
FT VFTNSDDDDVDVQLTGQVTEHLRNLQCSNGSATSPSTSVSASSSSARPLTNGNNHLSTA
FT SSTDTSLSLSERNNVPSPAPVPYSESAPQLKTFTGETPKLHPRSPFPPQPPVLPQRSKT
FT ASAVATTTTNPTTSNGAPPPVPGSKGPPVPPKPS -> MFQNSPMMYDWWNDTTKPKHQ
FT QPTLNVLSPWGAYFNHIGNELL (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057794"
FT VAR_SEQ 263..311
FT /note="SHLKIASSTVSSGCSSPQQYSSARSVGNSLSNGSVVSTTSSDGDVQLSN ->
FT S (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_057795"
FT MUTAGEN 388
FT /note="G->E: In cy2; probable loss of activity. Partial
FT sensitivity to the heavy metal Cu(2+). During development,
FT DD and DV motoneuron axons fail to reach the dorsal cord.
FT Axonal growth is not affected. Mild defect in locomotion.
FT In pak-1 mutants, causes lateral displacement of the VD
FT neuron. In mig-10 mutants, failure of HSN axons to migrate
FT to the ventral nerve cord."
FT /evidence="ECO:0000269|PubMed:17050621,
FT ECO:0000269|PubMed:18499456, ECO:0000269|PubMed:20008556"
FT MUTAGEN 405
FT /note="K->R: Probable loss of activity. Partial sensitivity
FT to the heavy metal Cu(2+) and loss of kgb-1 phosphorylation
FT upon Cu(2+) treatment. Does not affect interaction with
FT mlk-1."
FT /evidence="ECO:0000269|PubMed:20008556"
SQ SEQUENCE 646 AA; 70760 MW; F86CBA09E6830482 CRC64;
MSTSKSSKVR IRNFIGRIFS PSDKDKDRDD EMKPSSSAMD ISQPYNTVHR VHVGYDGQKF
SGLPQPWMDI LLRDISLADQ KKDPNAVVTA LKFYAQSMKE NEKTKFMTTN SVFTNSDDDD
VDVQLTGQVT EHLRNLQCSN GSATSPSTSV SASSSSARPL TNGNNHLSTA SSTDTSLSLS
ERNNVPSPAP VPYSESAPQL KTFTGETPKL HPRSPFPPQP PVLPQRSKTA SAVATTTTNP
TTSNGAPPPV PGSKGPPVPP KPSHLKIASS TVSSGCSSPQ QYSSARSVGN SLSNGSVVST
TSSDGDVQLS NKENSNDKSV GDKNGNTTTN KTTVEPPPPE EPPVRVRASH REKLSDSEVL
NQLREIVNPS NPLGKYEMKK QIGVGASGTV FVANVAGSTD VVAVKRMAFK TQPKKEMLLT
EIKVMKQYRH PNLVNYIESY LVDADDLWVV MDYLEGGNLT DVVVKTELDE GQIAAVLQEC
LKALHFLHRH SIVHRDIKSD NVLLGMNGEV KLTDMGFCAQ IQPGSKRDTV VGTPYWMSPE
ILNKKQYNYK VDIWSLGIMA LEMIDGEPPY LRETPLKAIY LIAQNGKPEI KQRDRLSSEF
NNFLDKCLVV DPDQRADTTE LLAHPFLKKA KPLSSLIPYI RAVREK
